Recent data from this laboratory suggest that the primate corpus luteum (CL) contains progesterone (P) and androgen (A) [but not estrogen (E)] receptors (R) and that the ovulatory gonadotropin surge induces PR in luteinizing granulosa cells. The proposed experiments are designed: (a) to investigate steroid R gene activity in the primate ovary and whether the midcycle gonadotropin surge increases PR mRNA levels in the developing corpus luteum, (b) to examine the role of gonadotropins (LH and CG) in the maintenance and """"""""rescue"""""""" of PR (but not AR or ER) in the CL of the menstrual cycle and early pregnancy, respectively, (c) to determine whether LH and CG act directly or indirectly [via prostaglandins (PGs) or steroids] to induce or maintain PR and its mRNA in luteal cells, and (d) to consider the role of progesterone/PR- and androgen/AR-mediated events in the development, function and regression of the primate corpus luteum during the menstrual cycle. Cells from pre- and post-ovulatory follicles and corpora lutea will be collected from rhesus monkeys at specific stages in spontaneous and artificial (gonadotropin-treated) menstrual cycles. GnRH antagonist and PG or steroid synthesis inhibitors (or vehicle) will be administered prior to tissue collection. Steroid Rs will be examined by immunocytochemistry, radioligand binding assays and Western blot analyses. Steroid R mRNAs will be detected by reverse transcription-polymerase chain reaction and PCR-amplified cDNA sequenced. Steroid R mRNAs will be quantitated by the ribonuclease protection assay. Cells will be cultured in the presence and absence of gonadotropins (FSH, LH, CG), PGs (e.g., PGE2 and F2alpha), steroids (P, A, E) or PG and steroid inhibitors to determine if LH/CG or gonadotropin-stimulated cell products directly regulate PR or mRNA expression. In vivo and cell culture approaches will determine if P and A act locally to modulate the development (including periovulatory events) and function (basal and LH/CG-sensitive PG and peptide synthesis) by the macaque corpus luteum. These studies should establish whether the primate corpus luteum of the menstrual cycle and early pregnancy contains classical steroid Rs and will likely identify a new action for luteotropic gonadotropins--the regulation of PR and hence P action. The first detailed investigation on the roles of P and A in the primate CL will be performed. This work should provide unique insight into gonadotropin-dependent, steroid-regulated processes that locally modulate primate luteal function, with direct applications to controlling fertility and infertility in women.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020869-09
Application #
2198112
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1985-07-01
Project End
1996-11-30
Budget Start
1994-12-01
Budget End
1995-11-30
Support Year
9
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Oregon Regional Primate Research Center
Department
Type
DUNS #
City
Beaverton
State
OR
Country
United States
Zip Code
97006
Bishop, Cecily V; Xu, Fuhua; Steinbach, Rosemary et al. (2017) Changes in immune cell distribution and their cytokine/chemokine production during regression of the rhesus macaque corpus luteum. Biol Reprod 96:1210-1220
Bishop, Cecily V; Hennebold, Jon D; Kahl, Christoph A et al. (2016) Knockdown of Progesterone Receptor (PGR) in Macaque Granulosa Cells Disrupts Ovulation and Progesterone Production. Biol Reprod 94:109
Bishop, Cecily V; Xu, Fuhua; Molskness, Theodore A et al. (2015) Dynamics of Immune Cell Types Within the Macaque Corpus Luteum During the Menstrual Cycle: Role of Progesterone. Biol Reprod 93:112
Bishop, Cecily V; Molskness, Theodore A; Xu, Fuhua et al. (2014) Quantification of dynamic changes to blood volume and vascular flow in the primate corpus luteum during the menstrual cycle. J Med Primatol 43:445-54
Bishop, C V; Aazzerah, R A; Quennoz, L M et al. (2014) Effects of steroid ablation and progestin replacement on the transcriptome of the primate corpus luteum during simulated early pregnancy. Mol Hum Reprod 20:222-34
Stouffer, Richard L; Bishop, Cecily V; Bogan, Randy L et al. (2013) Endocrine and local control of the primate corpus luteum. Reprod Biol 13:259-71
Bishop, C V; Satterwhite, S; Xu, L et al. (2012) Microarray analysis of the primate luteal transcriptome during chorionic gonadotrophin administration simulating early pregnancy. Mol Hum Reprod 18:216-27
Adam, M; Saller, S; Ströbl, S et al. (2012) Decorin is a part of the ovarian extracellular matrix in primates and may act as a signaling molecule. Hum Reprod 27:3249-58
Bishop, C V; Bogan, R L; Hennebold, J D et al. (2011) Analysis of microarray data from the macaque corpus luteum; the search for common themes in primate luteal regression. Mol Hum Reprod 17:143-51
Xu, Fuhua; Stouffer, Richard L; Muller, Jorg et al. (2011) Dynamics of the transcriptome in the primate ovulatory follicle. Mol Hum Reprod 17:152-65

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